Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Physiol Rev. 2011 Jul;91(3):1009-22. doi: 10.1152/physrev.00015.2010.
Inhibition in the adult mammalian central nervous system (CNS) is mediated by γ-aminobutyric acid (GABA). The fast inhibitory actions of GABA are mediated by GABA type A receptors (GABA(A)Rs); they mediate both phasic and tonic inhibition in the brain and are the principle sites of action for anticonvulsant, anxiolytic, and sedative-hypnotic agents that include benzodiazepines, barbiturates, neurosteroids, and some general anesthetics. GABA(A)Rs are heteropentameric ligand-gated ion channels that are found concentrated at inhibitory postsynaptic sites where they mediate phasic inhibition and at extrasynaptic sites where they mediate tonic inhibition. The efficacy of inhibition and thus neuronal excitability is critically dependent on the accumulation of specific GABA(A)R subtypes at inhibitory synapses. Here we evaluate how neurons control the number of GABA(A)Rs on the neuronal plasma membrane together with their selective stabilization at synaptic sites. We then go on to examine the impact that these processes have on the strength of synaptic inhibition and behavior.
在成年哺乳动物中枢神经系统（CNS）中，抑制作用由γ-氨基丁酸（GABA）介导。GABA 的快速抑制作用由 GABA 型 A 受体（GABA(A)Rs）介导；它们在大脑中介导着相性和紧张性抑制，是抗惊厥药、抗焦虑药和镇静催眠药（包括苯二氮䓬类、巴比妥类、神经甾体和一些全身麻醉药）的主要作用部位。GABA(A)Rs 是异五聚体配体门控离子通道，集中存在于抑制性突触后位点，在那里介导相性抑制，以及在突触外位点，在那里介导紧张性抑制。抑制作用的效力，因此神经元兴奋性，严重依赖于特定 GABA(A)R 亚型在抑制性突触上的积累。在这里，我们评估神经元如何控制神经元质膜上 GABA(A)R 的数量，以及它们在突触部位的选择性稳定。然后，我们继续研究这些过程对突触抑制和行为的影响。
